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高血压男性中内皮型一氧化氮合酶-786 T>C基因多态性与运动诱导的血压及一氧化氮反应

The endothelial nitric oxide synthase -786 T>C polymorphism and the exercise-induced blood pressure and nitric oxide responses among men with elevated blood pressure.

作者信息

Augeri Amanda L, Tsongalis Gregory J, Van Heest Jaci L, Maresh Carl M, Thompson Paul D, Pescatello Linda S

机构信息

Department of Kinesiology, University of Connecticut, Storrs, CT 06269-1110, USA.

出版信息

Atherosclerosis. 2009 Jun;204(2):e28-34. doi: 10.1016/j.atherosclerosis.2008.12.015. Epub 2008 Dec 16.

Abstract

OBJECTIVE

A polymorphism (-786 T>C) in the promoter region of the endothelial nitric oxide synthase gene (eNOS) has important functional characteristics. We examined the influence of eNOS -786 T>C (rs2070744) on the BP and NO response to acute dynamic exercise.

METHODS

Subjects (n=49, 43.7+/-1.4 yr) had pre- to Stage-1 hypertension (145.6+/-1.5/85.9+/-1.1 mmHg). Volunteers performed three experiments; a non-exercise control session, and two cycle exercise bouts at 40% (LIGHT) and 60% (MODERATE) of peak oxygen consumption. Subjects wore an ambulatory BP monitor upon leaving the laboratory. NO was measured by chemiluminescence assay before (baseline), during, and after the experiments. eNOS genotypes were determined by polymerase chain reaction and restriction enzyme digestion. Repeated measure ANOVA tested if BP and NO differed over time among experiments and by eNOS genotypes (n=25, TT; n=24, TC/CC).

RESULTS

Among carriers of the eNOS C(786) allele, systolic BP (SBP) was reduced 5.3+/-2.4 mmHg after MODERATE versus non-exercise control over 9h compared to those with the eNOS T786T genotype (p<0.05). Under these conditions, SBP tended to be lower 4.6+/-2.9 mmHg after LIGHT (p=0.076). The exercise-induced diastolic BP and NO responses were not different from non-exercise control between eNOS genotype (p>0.05).

CONCLUSION

Men who were carriers of the eNOS C(786) allele responded more favorably to the antihypertensive effects of aerobic exercise than men with the eNOS T786T genotype. The eNOS C(786) allele is associated with reduced eNOS gene transcription and promoter activity. Future work is needed to determine how exercise may override genetic predispositions to down regulate eNOS gene activity.

摘要

目的

内皮型一氧化氮合酶基因(eNOS)启动子区域的一种多态性(-786 T>C)具有重要的功能特性。我们研究了eNOS -786 T>C(rs2070744)对血压及急性动态运动时一氧化氮反应的影响。

方法

受试者(n = 49,43.7±1.4岁)患有1级高血压前期(145.6±1.5/85.9±1.1 mmHg)。志愿者进行了三项实验:一次非运动对照实验,以及两次分别为峰值耗氧量40%(轻度)和60%(中度)的自行车运动实验。受试者离开实验室时佩戴动态血压监测仪。在实验前(基线)、实验期间和实验后通过化学发光法测定一氧化氮。通过聚合酶链反应和限制性酶切确定eNOS基因型。重复测量方差分析用于检验实验之间以及不同eNOS基因型(n = 25,TT;n = 24,TC/CC)的血压和一氧化氮随时间的差异。

结果

与eNOS T786T基因型者相比,在携带eNOS C(786)等位基因者中,中度运动后9小时的收缩压(SBP)比非运动对照降低了5.3±2.4 mmHg(p<0.05)。在此条件下,轻度运动后SBP有降低4.6±2.9 mmHg的趋势(p = 0.076)。在eNOS基因型之间,运动诱导的舒张压和一氧化氮反应与非运动对照无差异(p>0.05)。

结论

携带eNOS C(786)等位基因的男性比eNOS T786T基因型的男性对有氧运动的降压作用反应更良好。eNOS C(786)等位基因与eNOS基因转录和启动子活性降低有关。需要进一步研究以确定运动如何克服遗传易感性来下调eNOS基因活性。

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